Cytokine release, small airway injury, and parenchymal damage during mechanical ventilation in normal open-chest rats

Edgardo D'Angelo, Antonia Koutsoukou, Patrizia Della Valle, Guendalina Gentile, Matteo Pecchiari

Research output: Contribution to journalArticlepeer-review


Lung morpho-functional alterations and inflammatory response to various types of mechanical ventilation (MV) have been assessed in normal, anesthetized, openchest rats. Measurements were taken during protective MV [tidal volume (VT) = 8 ml/kg; positive end-expiratory pressure (PEEP) = 2.6 cmH2O] before and after a 2- to 2.5-h period of ventilation on PEEP (control group), zero EEP without (ZEEP group) or with administration of dioctylsodiumsulfosuccinate (ZEEP-DOSS group), on negative EEP (NEEP group), or with large VT (26 ml/kg) on PEEP (Hi-VT group). No change in lung mechanics occurred in the Control group. Relative to the initial period of MV on PEEP, airway resistance increased by 33 ± 4, 49 ± 9, 573 ± 84, and 13 ± 4%, and quasi-static elastance by 19 ± 3, 35 ± 7, 248 ± 12, and 20 ± 3% in the ZEEP, NEEP, ZEEP-DOSS, and Hi-VT groups. Relative to Control, all groups ventilated from low lung volumes exhibited histologic signs of bronchiolar injury, more marked in the NEEP and ZEEP-DOSS groups. Parenchymal and vascular injury occurred in the ZEEP-DOSS and Hi-VT groups. Pro-inflammatory cytokine concentration in the bronchoalveolar lavage fluid (BALF) was similar in the Control and ZEEP group, but increased in all other groups, and higher in the ZEEP-DOSS and Hi-VT groups. Interrupter resistance was correlated with indexes of bronchiolar damage, and cytokine levels with vascular-alveolar damage, as indexed by lung wet-to-dry ratio. Hence, protective MV from resting lung volume causes mechanical alterations and small airway injury, but no cytokine release, which seems mainly related to stress-related damage of endothelial-alveolar cells. Enhanced small airway epithelial damage with induced surfactant dysfunction or MV on NEEP can, however, contribute to cytokine production.

Original languageEnglish
Pages (from-to)41-49
Number of pages9
JournalJournal of Applied Physiology
Issue number1
Publication statusPublished - Jan 2008


  • Inflammation
  • Lung mechanics
  • Microvascular damage
  • Recruitment-derecruitment of lung units

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation


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